Benzenesulfonic acid, 4-C20-24 (even numbered) sec-alkyl derivs., sodium salts

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented peer-reviewed journal article by researchers at GLP contract testing laboratory.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1975

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Twenty female mice were administered 0.2, 2.0, 300 or 600 mg/kg bw of LABS Na by gavage at days 6-15 of gestation. All animals were sacrificed on day 17 of pregnancy.

GLP compliance:

yes

Remarks:

not stated, but likely GLP

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Benzenesulfonic acid, C10-13-alkyl derivs., sodium salts

EC Number:

270-115-0

EC Name:

Benzenesulfonic acid, C10-13-alkyl derivs., sodium salts

Cas Number:

68411-30-3

IUPAC Name:

sodium 4-undecylbenzenesulfonate

Test material form:

solid

Specific details on test material used for the study:

Supplied by Lion Fat & Oil Co., Tokyo

Test animals

Species:

mouse

Strain:

CD-1

Details on test animals or test system and environmental conditions:

Mice were held in plastic containers at standard environmental conditions (20 =/- 1 degrees C, 50 =/- 5% relative humidity) and free access to drinking water and food (Spratt's Laboratory Diet No. 1).

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on exposure:

Dosing commenced on day 6 after confirmation of mating by detection of the vaginal plug. Exposure continued until day 15 of gestation.

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

Male and female mice were housed five per cage in opaque plastic cages until natural mating occurred.

Duration of treatment / exposure:

days 6 - 15 of pregnancy

Frequency of treatment:

daily

Duration of test:

sacrifice at day 17 of pregnancy

No. of animals per sex per dose:

20 female mice per dose

Control animals:

yes, concurrent no treatment

Details on study design:

Two doses were chosen to form the basis for safety evaluation (0.2 and 2.0 mg/kg/day) because the likely maximum human intake of detergent from ordinary kitchen use has been estimated at 0.14 mg/kg/day, thus providing factors of 1-2 times the human exposure level. Two further doses were also investigated (300 and 600 mg/kg/day) based on previous toxicity data suggesting that these would impair maternal survival and result in obvious adverse effects.

Examinations

Maternal examinations:

All animals were observed daily for signs of malreaction and were weighed regularly throughout gestation. All animals that died, and survivors at termination, were dissected and examined for macroscopic changes.

Ovaries and uterine content:

Ovaries were examined and the number of corpora lutea counted.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Among parent animals, treatment at 300 and 600 mg/kg bw d was associated with increased mortality (35% and 90% respectively). At 300 mg/kg bw d weight gain was retarded only during the first four days. No assessment could be made at 600 mg/kg bw d, due to the high mortality rate. Necropsy revealed a ubiquitous occurrence of tympanites, sometimes associated with gastritis. Pregnancy rate was essentially comparable for all groups.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

2 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Maternal abnormalities

Abnormalities:

not specified

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
At doses with no maternal toxicity, no differences were observed among the dose group and the control group with respect to number of litters, viable young, litter weight, foetal weight, embryonic deaths, implantations and post implantation embryonic loss. At these doses the incidences of major malformations and minor abnormalities were not affected. At the 300 mg/kg bw/day dose, the incidence of total liter loss was 20%; this was attributed to the high maternal toxicity observed at this dose. Among the nine animals with viable young at this dose, mean litter parameters, including litter size and fetal loss, and incidence of major malformations were not statistically different from controls. Minor anomilies, including gross or visceral and skeletal anomalies were increased. At the 600 mg/kg dose, there were no live births.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

300 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

The maternal NOAEL of 2 mg/kg bw d is considered very conservative because the range (2-300 mg/kg bw d) was too wide, especially considering the repeated dose toxicity studies (section 7.5.1) which give much higher NOAEL values.

Applicant's summary and conclusion

Conclusions:

Maternal NOAEL = 2 mg/kg bw/day; Teratogenicity NOAEL = 300 mg/kg bw/day

Executive summary:

Pregnant female mice were exposed to LAS via gavage on days 6 -15 of gestation. Increased mortality was observed at the two highest doses (300 and 600 mg/kg bw/day). These doses also exhibited retarded weight gain and adverse signs in the necropsy. Pregnancy was comparable, however, for all groups. At doses without maternal toxicity, no differences were observed in any parameters. Because of the very wide range between the 2 mg/kg and 300 mg/kg doses, the maternal NOAEL of 2 mg/kg bw/day must be considered very conservative. The NOAEL for teratogenicity was 300 mg/kg bw/day.